The Role of the ADAMTS Proteins in the Intervertebral Disc

Abstract

Proteinases (often referred to as proteases) are enzymes that hydrolyze the peptide bonds that hold amino acids together within a polypeptide (protein) molecule. Secreted and cell-surface proteinases are indispensable in several processes, such as digestion, molecular maturation, or activation of precursor proteins (proproteins), and in the turnover of diverse cellular products such as cell-surface receptors and extracellular matrix (ECM) proteins and proteoglycans. These last two functions are highly relevant to the skeletal system, which comprises ECM proteins, including proproteins such as procollagens, as quantitatively major components having an indispensable structural role. In addition, the ECM is increasingly being recognized for its role in regulating cell behavior, such as in signaling through cell-matrix adhesion molecules, and proteolytic products of ECM (matrikines). Proteinases are required for and participate in all major phases of vertebrate life, e.g., during embryonic development, they are required for rapid tissue remodeling, whereas in the adult organism, they participate in essential homeostatic processes, such as coagulation, or adaptive responses to biomechanical fluxes, e.g., bone and connective tissue remodeling in response to mechanical stress. They are recognized to have diverse, complex roles in the origin and/or resolution of inflammatory, degenerative, and malignant disorders. Indeed, proteinases, including ADAMTS proteinases, are frequently targeted for drug development because of their pivotal role in diseases (Fosang and Little 2008).